Psychedelic Medicine Podcast with Dr. Lynn Marie Morski · Lynn Marie Morski, MD, JD

Understanding Psychedelics and Neuroplasticity with Robin Carhart-Harris, PhD

June 12, 2025·45 min·4 clips

Robin Carhart-Harris reveals how chronic stress withers brain neurons like an unhealthy tree, a key driver of depression.

Dr. Lynn Marie Morski hosts Dr. Robin Carhart-Harris, a leading neuroscientist and founder of the Center for Psychedelic Research at Imperial College London. This episode explores the relationship between psychedelic substances and the brain's capacity for change. Carhart-Harris defines neuroplasticity as the brain's inherent changeability, not change itself. He explains that chronic stress reliably causes brain atrophy, seen in reduced gray matter density in humans and shrunken neuronal dendrites in animal studies. This stress-induced atrophy is a major contributor to mental illness, potentially creating rigid neural pathways, a process termed canalization. He introduces his "snow globe" metaphor, where psychedelics shake up these overly reinforced pathways to enable recalibration. Neuroplasticity here differs from neurogenesis, as psychedelics primarily promote synaptogenesis, the growth of new synaptic connections, not new neurons. Research in mice shows substances like psilocybin increase dendritic spine density in the cortex, with longer-lasting trips generally producing more enduring effects. The serotonin 2A receptor is key for classic psychedelics to stimulate this cortical synaptogenesis. Carhart-Harris contrasts this with ketamine, which acts on the glutamate system and produces a shorter plasticity window, and MDMA, which promotes serotonin release and prosocial feelings. A surprising insight is that serotonin 2A receptor stimulation in utero helps control the growth of the cortex. Carhart-Harris links increased brain entropy—a measure of randomness and disorder—under psychedelics directly to richer conscious experience. He describes the default mode network as a brain system active during introspection and daydreaming, which becomes dysregulated during psychedelic experiences. This dysregulation may relate to the subjective phenomenon of ego dissolution. Early human brain imaging work from his team showed the default mode network becoming desynchronized under psilocybin. Preliminary findings suggest psilocybin therapy for depression can decrease the segregated, modular organization of brain networks, making the brain more globally interconnected. The tone is deeply educational and conversational, with the host facilitating a detailed exploration of complex neuroscience. Carhart-Harris employs accessible analogies, like the snow globe and a fresh snowfall, to explain intricate concepts. Listeners interested in the biological mechanisms behind psychedelic therapy and cutting-edge neuroscience will find this episode compelling. Those seeking only personal stories or clinical guidelines without scientific depth might find it too technical.

As heard by us

A careful look at how psychedelics may affect the cortex, with the evidence kept front and center.

Robin Carhart-Harris and Dr. Lynn-Marie Morski keep the focus on how psychedelics may connect to neuroplasticity, moving from Brian Roth's receptor pharmacology and early synaptogenesis findings to David Olson's later work on cortical change.

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If you want a careful look at psychedelics and neuroplasticity, start here.

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